In the broadest sense, we would like to determine the fundamental principles from which proteins derive their function. This requires an appreciation of the essentials of polypeptide folding and the requirements of enzymic catalysis. The former refers to the formation of the architectural framework while the latter relates to the decorations which provide the functional properties. We have shown that a good approach to both these problems is by a comparison of different proteins in order to discover the common (and hence important) features. We are pursuing these studies explicitly by investigating the three-dimensional structure of various nucleotide binding proteins and one heme binding protein using X-ray crystallography. Our present work can be subdivided as follows. A. Lactate Dehydrogenase. We have under investigation four distinct structures. a. Apo M4 LDH from dogfish: The 2.0 A resolution refinement is drawing to a close. b. Ternary complexes (LDH:coenzyme:substrate) of M4 LDH from dogfish: The structure determined to 3.0 A resolution must be extended to 2.0 A resolution. The data have been collected. c. Ternary complexes (LDH:coenzyme:substrate) of H4 LDH from pig: A 2.5 A resolution structure requires refinement. d. Apo LDH-X mouse: A 2.9 A resolution map needs to be analyzed. B. Glyceraldehyde-3-Phosphate Dehydrogenase. Two structures of the lobster enzyme are under investigation. a. The holo-enzyme: A variety of NAD and NAD:substrate analogue studies need to be refined. The data should be extended from 2.9 to 2.0 A resolution. b. The apo-enzyme: Data collection is commencing. C. Glutamate Dehydrogenase (tuna fish), Glycerol-3-Phosphate Dehydrogenase (rabbit), and Quinolinate Phosphoribosyltransferase (pig liver). Structural investigations of these nucleotide binding enzymes are just starting. D. Catalase. A high resolution structure is anticipated next year.